Dityrosine bridge formation and thyroid hormone synthesis are tightly linked and are both dependent on N‐glycans

FEBS Letters

Niccoli, Patricia¹  Carayon, Pierre¹  Lejeune, Pierre-Jean¹  Mallet, Bernard¹  Vinet, Liliane¹  Baudry, Nathalie¹ 

[1] Unité 38 INSERMé de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France

关键词: Thyroid;    Hormone synthesis;    Glycosylation;    Dityrosine;    Tg;    thyroglobulin;    T3;    triiodothyronine;    T4;    thyroxine;    MIT;    monoiodotyrosine;    DIT;    diiodotyrosine;    TPO;    thyroperoxidase;    LPO;    lactoperoxidase;    ConA;    concanavalin A;    RCA120;    Ricinus communis agglutinin;    SDS-PAGE;    sodium dodecyl sulfate polyacrylamide gel electrophoresis;   

DOI  :  10.1016/0014-5793(96)01107-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Formation of dityrosine bridges is a ubiquitous process mainly attributed to oxidative stress leading to protein degradation and cellular damages. Here we show that dityrosine formation is involved in a physiological process, thyroid hormone synthesis, and is strictly dependent on structural characteristics, namely N-glycans, presented by the protein acting as the prothyroid hormone. We used two isoforms of the N-terminal thyroid hormone forming domain (NTD) of human thyroglobulin: one without N-glycan (19 kDa isoform) and the other with high mannose type structures (25 kDa isoform). Both isoforms were able to form iodotyrosines after in vitro iodination. However, iodotyrosine coupling to form thyroxine did not occur with the unglycosylated 19 kDa NTD. In contrast, the 25 kDa isoform formed thyroxine. Strikingly, thyroxine synthesis was accompanied by dimerization of the 25 kDa isoform and formation of a dityrosine bridge; none of this was observed with the 19 kDa isoform. Taken as a whole, our results indicate that dimerization through dityrosine bridging accompanies and could have a role in thyroid hormone synthesis.

【 授权许可】

Unknown